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<jats:title>Dynamics of cell signaling and decoding</jats:title> <jats:p> Defects in cellular signaling pathways, like those in some cancer cells, are often thought to result in increased or decreased steady-state signals that promote or inhibit cell proliferation. But Bugaj <jats:italic>et al.</jats:italic> show that dynamic changes in the duration or frequency of a signal can also alter cellular responses (see the Perspective by Kolch and Kiel). They took precise control of signaling in cultured human or mouse cells with a light-controlled mechanism for activating and inactivating the guanosine triphosphate Ras. Known cancer mutations in components of the Ras-activated signaling pathway or inhibitors of particular pathway components altered signal timing and readouts. The modified dynamics changed transcriptional outcomes and could inappropriately support cell proliferation. The ability to probe responses of signaling networks in this way may enhance understanding of biological regulation and reveal new therapeutic targets. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" related-article-type="in-this-issue" xlink:href="10.1126/science.aao3048">eaao3048</jats:related-article> ; see also p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6405" page="844" related-article-type="in-this-issue" vol="361" xlink:href="10.1126/science.aau8059">844</jats:related-article> </jats:p>

<jats:title>Looping together genes in cancer</jats:title> <jats:p> A subset of human cancers are characterized by aberrant fusion of two specific genes. In some cases, the activity of the resultant fusion protein drives tumor growth. Most fusion genes in cancer appear to arise from simple reciprocal chromosomal translocations. Anderson <jats:italic>et al.</jats:italic> found that the characteristic fusion gene in a bone and soft tissue tumor called Ewing sarcoma is produced by a far more complicated mechanism (see the Perspective by Imielinski and Ladanyi). In nearly half of the tumors examined, the fusion gene was created by the formation of dramatic genomic loops that disrupt multiple genes. These complex rearrangements occur in early replicating and transcriptionally active regions of the genome and are associated with poor prognosis. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" related-article-type="in-this-issue" xlink:href="10.1126/science.aam8419">eaam8419</jats:related-article> ; see also p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6405" page="848" related-article-type="in-this-issue" vol="361" xlink:href="10.1126/science.aau8231">848</jats:related-article> </jats:p>

<jats:p> Best <jats:italic>et al</jats:italic> . claim that we provide no convincing basis to assert that a discrepancy remains between FRET and SAXS results on the dimensions of disordered proteins under physiological conditions. We maintain that a clear discrepancy is apparent in our and other recent publications, including results shown in the Best <jats:italic>et al</jats:italic> . comment. A plausible origin is fluorophore interactions in FRET experiments. </jats:p>

<jats:p> Riback <jats:italic>et al</jats:italic> . (Reports, 13 October 2017, p. 238) used small-angle x-ray scattering (SAXS) experiments to infer a degree of compaction for unfolded proteins in water versus chemical denaturant that is highly consistent with the results from Förster resonance energy transfer (FRET) experiments. There is thus no “contradiction” between the two methods, nor evidence to support their claim that commonly used FRET fluorophores cause protein compaction. </jats:p>